Impact of angiogenesis and antiangiogenic therapies to tumor progression. Angiogenesis is thought to promote tumor growth though the delivery of oxygen and nutriments to the growing tumor, but evidence suggests that additional mechanisms may be involved. We are interested in unraveling paracrine effects of angiogenic vessels on primary tumor growth, tumor invasion and metastasis formation. One signaling pathways we are analyzing is the Akt/PKB pathway, which has potent angiogenic activity. Furthermore, while it has been traditionally assumed that antiangiogenic treatments will not face the problems of resistance as observed during chemotherapy, emerging evidence indicates that indeed tumors can escape angiogenic blockade. We are interested in identifying mechanisms of escape and new molecules as candidate therapeutic targets to prevent/treat escape.
Monitoring tumor angiogenesis. A main question and challenge in the field of clinical anti-angiogenesis research is how to improve the monitoring of antiangiogenic drugs tested in clinical trials. The efficacy of conventional anticancer agents is commonly evaluated by measuring their direct effect on tumor size (i.e. response rate), and ultimately survival (i.e. prolongation of time to progression and time to death). To assess an antiangiogenic effect the response rate is an inadequate endpoint. Since the antitumor effect of antiangiogenic drugs is indirect we need to be able to assess the biological effects on the tumor vasculature independently of the overall antitumor activity and clinical response. New surrogate markers of angiogenesis and/or antiangiogenic activity need to be identified and subsequently validated. Many approaches to quantify tumor angiogenesis in patients in a non-invasive and reliable manner are being considered and investigated. We are currently exploring cellular, biochemical and functional markers of angiogenesis in experimental cancer models and in cancer patients.